In recent years a number of compounds for the treatment of hair loss have been developed, including minoxidil (Rogaine.RTM.). Hair loss treatment with such compounds is generally provided by delivery of the active ingredient or ingredients through the skin, i.e. transdermally, as opposed to other methods of parenteral administration. The large surface area of the skin and the extensive circulatory and lymphatic networks available near the skin surface make topical application of drugs for treatment of hair loss extremely desirable. Moreover, topical application of drugs is relatively non-invasive, convenient, proven to be safe and provides greater control over delivery of active agents to the desired target site.
However, in order to be effective, an active agent for hair treatment must pass through the outer layer of skin or epidermis and into the dermis layer before being absorbed into the bloodstream. The epidermis comprises two main parts, the stratum corneum and the stratum germinativum. The stratum corneum forms the outermost layer of the epidermis and consists of many stratified layers of compacted, flattened, keratinized cells which have lost their nuclei. This outermost layer serves as a physical barrier to microorganisms and most chemical agents. In particular, it behaves as a primary barrier to percutaneous absorption of drugs. Because of the barrier effect of the skin, it has heretofore only been possible to deliver drugs that are "low-dose" drugs, i.e. in the range of 15 mg/day or less, or those of low molecular weight. In addition, drugs for transdermal delivery must have the proper lipophilic-hydrophilic balance to permit adequate absorption. As early as the beginning of this century it has been known that lipid-soluble substances, such as non-electrolytes have a comparatively greater skin permeability than water-soluble substances, such as electrolytes.
Percutaneous absorption or transdermal permeation is basically a composite of a series of steps in sequence. A penetrant molecule is first absorbed onto the surface layers of the stratum corneum, diffuses through the stratum corneum and the viable epidermis below, and finally diffuses through the papillary dermis and into the microcirculation.
Diffusional resistance of the stratum corneum to topically applied agents has been demonstrated with various drugs. In order to overcome this barrier effect a number of compounds have been developed which enhance the transdermal delivery of drugs, such as dimethyl sulfoxide (DMSO), polyethylene glycol monolaurate, alkyl lactams, long chain amides, and substituted 1,3-dioxacyclopentanes and substituted 1,3-dioxacyclohexanes. For example, U.S. Pat. No. 3,551,554 discloses DMSO, U.S. Pat. No. 3,989,816 discloses 1-substituted azacycloheptane-2-one, U.S. Pat. No. 4,132,781 discloses a topical antibiotic composition containing 2-pyrrolidone or an n-lower alkyl-2-pyrrolidone, U.S. Pat. No. 4,017,641 discloses propylene glycol and 2-pyrrolidone-containing compositions and U.S. Pat. No. 4,861,764 discloses 1,3-dioxolane and 1,3-dioxane derivatives as percutaneous absorption enhancers. WO 92/16236 discloses methods and compositions for enhancing the rate of absorption of topically administered physiologically active compounds. Minoxidil is disclosed as one of these compounds. The penetration enhancers are amino alcohol derivatives which may form a 1,3-dioxane ring.
Therapy of age related hair loss in androgenic alopecia patients with topical solutions of minoxidil (Rogaine.RTM.) alone, or in combination with skin penetration enhancers, such as DMSO, has resulted in only moderate to dense regrowth of hair in less than 40% of such patients (Katz, H. I., Clin. Dermatol., 6:195-199, 1988). Moreover, treatments with topical solutions of minoxidil require multiple applications of the active ingredient each day, which can be very inconvenient as well as expensive. Androgenic alopecia or common baldness represents 99 percent of all cases of hair loss (Brodland and Muller, Cutis, 47:173-176, 1991) and, therefore, there is a need for improved compositions and methods for treating hair loss in patients with age related baldness. In particular, there is a need for methods of treating hair loss that require fewer applications of active ingredient, e.g. minoxidil, and which will also provide hair regrowth sooner, in more abundance, and thicker, than is presently observed using minoxidil and known penetration enhancers.
It is therefore, an object of the present invention to provide a treatment for hair loss that is safe, simple, easy to apply, and inexpensive when compared to other hair loss treatments.
It is also an object of the present invention to provide a treatment for hair loss that provides faster and more abundant hair regrowth than conventional treatments, using fewer applications of minoxidil and using the same concentration of minoxidil per treatment as is conventionally used.